Pain
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The mechanisms underlying chemotherapy-induced peripheral neuropathy have yet to be fully elucidated, but primary afferent neurons have emerged as an especially vulnerable initiating pathophysiological target. An important recent study has also shown that the initial toxicity produced by paclitaxel in patients was highly predictive of long-term outcome. In this study, we therefore focused on defining the mechanisms of acute toxicity produced by paclitaxel treatment on primary sensory neurons under in vitro conditions. ⋯ However, CCL2 applied to cultured neurons not only induced DSFs but also evoked action potentials. Evidence of oxidative stress and mitotoxicity was observed at 48 hours of exposure. These results closely parallel the responses measured in the DRG with paclitaxel exposure in vivo and so indicate that acute toxicity of paclitaxel on the DRG can be modelled using an in vitro approach.
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Few studies all based on classical surveys have provided prevalence estimates of chronic pain (CP) in opioid-maintained patients (OMPs) but often had a limited patient sample size and a great variability in the prevalence estimates. This study sought to assess the prevalence of CP in the exhaustive population of OMPs using the capture-recapture method applied to the French nationwide health care database. Capture-recapture methods are increasingly used to estimate the prevalence of chronic conditions but have never been used in the specific context of CP in OMPs. ⋯ Most patients were male (67%) in OMPs and non-OMPs; median ages for OMPs and non-OMPs were 46 (interquartile range: 38-51) and 48 (41-53) years, respectively. The CP prevalence estimated in OMPs and non-OMPs ranged from 23.6% (14.9-46.2) to 32.1% (28.6-36.3) and from 7.28% (3.98-18.4) to 9.32% (7.42-12.1), respectively. This first study on CP in the exhaustive population of OMPs using the capture-recapture method demonstrated a high prevalence of CP in OMPs, 3- to 4-fold than in the general population.
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Endometriosis affects ∼176 million women worldwide, yet on average, women experience pain ∼10 years from symptom onset before being properly diagnosed. Standard treatments (drugs or surgery) often fail to provide long-term pain relief. Elevated levels of reactive aldehydes such as 4-hydroxynonenal (4-HNE) have been implicated in the peritoneal fluid of women with endometriosis and upon accumulation, reactive aldehydes can form protein-adducts and/or generate pain. ⋯ We determined, in the eutopic and ectopic endometrium of women with severe (stage IV) peritoneal endometriosis, that ALDH2 enzyme activity was decreased, which was associated with decreased ALDH2 expression and increased 4-HNE adduct formation compared to the eutopic endometrium of controls in the proliferative phase. Using a rodent model of endometriosis and an ALDH2*2 knock-in mouse with decreased ALDH2 activity, we determined that increasing ALDH2 activity with the enzyme activator Alda-1 could prevent endometriosis lesion development as well as alleviate pain-associated behaviors in proestrus. Overall, our findings suggest that targeting the ALDH2 enzyme in endometriosis may lead to better treatment strategies and in the proliferative phase, that increased 4-HNE adduct formation within the endometrium may serve as a less invasive diagnostic biomarker to reduce years of suffering in women.
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Low back pain (LBP) is a high-burden condition that lacks routine surveillance data. Health administrative data may be used for surveillance, but their validity for measuring LBP in the general population has not been established. We aimed to (1) determine the validity of health administrative data to measure LBP compared to self-reported LBP in a population-based sample of Ontario adults; and (2) describe the differences in characteristics of LBP cases based on data sources. ⋯ Characteristics of LBP cases based on data sources differed in sex, health/behaviour characteristics, and allied health care utilization. Using health administrative data significantly underestimates the prevalence of LBP. This can lead to misclassification bias that is likely nondifferential in epidemiological studies.
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The differentiation of chronic primary pain syndromes into those with widespread vs regional musculoskeletal pain has been characterized by controversial discussions about common or distinct mechanisms and core clinical and sensory criteria. For example, the recent revision of fibromyalgia criteria has discarded sensory characteristics such as number of "tender points." This study examined empirical evidence related to this diagnostic shift and aimed to identify basic sensory-clinical pain phenotypes in patients with chronic local primary pain (chronic primary back pain [CBP]) and patients with chronic widespread primary pain (fibromyalgia syndrome). Combined sensory-clinical pain phenotypes of 185 patients with previous CBP and fibromyalgia syndrome diagnoses were derived by a stepwise data reduction through descriptive statistical, correlational, principal components and latent class analyses. ⋯ Subsequent discriminant analysis revealed that 3 discriminant functions of pressure sensitivity markers sufficed to differentiate the clusters. These sensory-clinical phenotypes differed also in somatic symptoms and impairment but neither in psychopathology nor in psychosocial cofactors. The results highlight the relevance of sensory testing in combination with clinical pain assessment in chronic primary pain syndromes.